chr5-177604405-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007255.3(B4GALT7):​c.277C>G​(p.His93Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H93Y) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

B4GALT7
NM_007255.3 missense

Scores

10
6
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.11
Variant links:
Genes affected
B4GALT7 (HGNC:930): (beta-1,4-galactosyltransferase 7) This gene is a member of the beta-1,4-galactosyltransferase (beta4GalT) family. Family members encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. Each beta4GalT member has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus which then remains uncleaved to function as a transmembrane anchor. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage (GlcA-beta1,3-Gal-beta1,3-Gal-beta1,4-Xyl-beta1-O-Ser) found in proteoglycans. This enzyme differs from other beta4GalTs because it lacks the conserved Cys residues found in beta4GalT1-beta4GalT6 and it is located in cis-Golgi instead of trans-Golgi. Mutations in this gene have been associated with the progeroid form of Ehlers-Danlos syndrome. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
B4GALT7NM_007255.3 linkuse as main transcriptc.277C>G p.His93Asp missense_variant 2/6 ENST00000029410.10 NP_009186.1 Q9UBV7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
B4GALT7ENST00000029410.10 linkuse as main transcriptc.277C>G p.His93Asp missense_variant 2/61 NM_007255.3 ENSP00000029410.5 Q9UBV7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
48
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.75
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;.
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Uncertain
0.087
D
MetaRNN
Pathogenic
0.82
D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Pathogenic
3.4
M;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-6.9
D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;.
Vest4
0.89
MutPred
0.59
Gain of relative solvent accessibility (P = 0.0249);.;
MVP
0.50
MPC
0.74
ClinPred
1.0
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.86
gMVP
0.92

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142476892; hg19: chr5-177031406; API